A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis
A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis
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DOI：
10.1111/j.1365-2036.2005.02420.x
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发表时间：
2005-04-01
影响因子：
7.6
通讯作者：
Lavine, JE
中科院分区：
文献类型：
--
作者：
Schwimmer, JB;Middleton, MS;Lavine, JE
背景：非酒精性脂肪性肝炎的儿童存在胰岛素抵抗，二甲双胍已被提出作为一种潜在的治疗方法。目的：验证二甲双胍治疗儿童非酒精性脂肪性肝炎可安全改善肝病标志物的假设。方法：对非糖尿病非酒精性脂肪性肝炎患儿进行单臂开放标签试验，每天2次，每次500 mg，疗程24周。结果：10名肥胖儿童(平均体重指数30.4)入选并完成试验。平均丙氨酸氨基转移酶和天冬氨酸氨基转移酶从治疗前(184,114U/L)到治疗结束(98，68U/L)均有显著改善(P<0.01)。40%的受试者丙氨酸转氨酶恢复正常，50%的受试者AST恢复正常。磁共振波谱测量的肝脏脂肪(30-23%，P<；0.01)，定量胰岛素敏感性检查指数(0.294-0.310，P<；0.05)测量的胰岛素敏感性，以及儿童生活质量问卷4(69-81，P<；0.01)测量的生活质量均有显著改善。结论：二甲双胍开放治疗24周可显著改善肝脏化学、肝脏脂肪、胰岛素敏感性和生活质量。需要一项大型随机对照试验来确定二甲双胍对儿科非酒精性脂肪性肝炎的疗效。
Background: Children with non-alcoholic steatohepatitis are insulin-resistant and metformin has been proposed as a potential therapy. However, paediatric safety and efficacy data are absent.Aim: To test the hypothesis that metformin therapy will safely improve markers of liver disease in paediatric non-alcoholic steatohepatitis.Methods: Single-arm open-label pilot study of metformin 500 mg twice daily for 24 weeks in non-diabetic children with biopsy-proven non-alcoholic steatohepatitis.Results: Ten obese children (mean body mass index 30.4) enrolled and completed the trial. Mean alanine aminotransferase and aspartate aminotransferase (AST) improved significantly (P < 0.01) from baseline (184, 114 U/L) to end of treatment (98, 68 U/L). Alanine aminotransferase normalized in 40% and AST normalized in 50% of subjects. Children demonstrated significant improvements in liver fat measured by magnetic resonance spectroscopy (30-23%, P < 0.01); insulin sensitivity measured by quantitative insulin sensitivity check index (0.294-0.310, P < 0.05); and quality of life measured by pediatric quality of life inventory 4.0 (69-81, P < 0.01).Conclusion: Open-label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life. A large randomized-controlled trial is needed to definitively determine the efficacy of metformin for paediatric non-alcoholic steatohepatitis.